CD4<sup>+</sup>T cells derived from B cell-deficient mice inhibit the establishment of peripheral B cell pools

Baumgarth, Nicole; Jager, Gina C.; Herman, Ometa C.; Herzenberg, Leonard A.; Herzenberg, Leonore A.

doi:10.1073/pnas.97.9.4766

Cited by 34 publications

(38 citation statements)

References 45 publications

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“…from GalT Ϫ/Ϫ mice did not lead to anti-Gal IgM production in the undepleted recipient GalT Ϫ/Ϫ , Ϫ/Ϫ mice, consistent with the results of Baumgarth et al (18). However, CD4…”

Section: Peritoneal Cavity Cells From Galt ϫ/ϫ Mice Have High Potentisupporting

confidence: 82%

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Peritoneal Cavity B Cells Are Precursors of Splenic IgM Natural Antibody-Producing Cells

Kawahara

Ohdan

Zhao

et al. 2003

The Journal of Immunology

137

105

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Peritoneal cavity B-1 cells are believed to produce IgM natural Abs. We have used α1,3-galactosyltransferase-deficient (GalT−/−) mice, which, like humans, produce IgM natural Abs against the carbohydrate epitope Galα1,3Gal (Gal), to demonstrate that peritoneal cavity B-1b cells with anti-Gal receptors produce anti-Gal IgM Abs only after LPS stimulation. Likewise, peritoneal cavity cells of GalT−/− and wild-type mice do not produce IgM Abs of other specificities without LPS stimulation. Development of Ab-secreting capacity is associated with loss of CD11b/CD18 (Mac-1) expression. In contrast, there are large numbers of cells producing anti-Gal and other IgM Abs in fresh splenocyte preparations from GalT−/− and (for non-Gal specificities) wild-type mice. These cells are Mac-1− but otherwise B-1b-like in their phenotype. We therefore hypothesized a pathway wherein peritoneal cavity B cells migrate into the spleen after activation in vivo and lose Mac-1 expression to become IgM Ab-producing cells. Consistent with this possibility, splenectomy reduced anti-Gal Ab production after immunization of GalT−/− mice with Gal-positive rabbit RBC. Furthermore, splenectomized B6 GalT−/−, Ig μ-chain mutant (μ−/−) (both Gal- and B cell-deficient) mice produced less anti-Gal IgM than nonsplenectomized controls after adoptive transfer of peritoneal cavity cells from B6 GalT−/− mice. When sorted GalT−/− Mac-1+ peritoneal cavity B cells were adoptively transferred to B6 GalT−/−, μ−/− mice, IgM Abs including anti-Gal appeared, and IgM-producing and Mac1− B cells were present in the spleen 5 wk after transfer. These findings demonstrate that peritoneal cavity Mac-1+ B-1 cells are precursors of Mac-1− splenic IgM Ab-secreting cells.

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“…from GalT Ϫ/Ϫ mice did not lead to anti-Gal IgM production in the undepleted recipient GalT Ϫ/Ϫ , Ϫ/Ϫ mice, consistent with the results of Baumgarth et al (18). However, CD4…”

Section: Peritoneal Cavity Cells From Galt ϫ/ϫ Mice Have High Potentisupporting

confidence: 82%

“…ϩ T cell-depleted recipients of PerC cells (data not shown), also consistent with previous studies (18). Thus, the initial presence of CD4 ϩ T cells derived from Ϫ/Ϫ mice inhibited the engraftment of PerC B cells.…”

Section: Cd4supporting

confidence: 80%

Peritoneal Cavity B Cells Are Precursors of Splenic IgM Natural Antibody-Producing Cells

Kawahara

Ohdan

Zhao

et al. 2003

The Journal of Immunology

137

105

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“…Adult NOD.K null mice could not be reconstituted with B cells from NOD.K ϩ mice (Table III, lines 6 and 7, and data not shown), presumably because the transferred B cells were rejected by CD8 ϩ T cells (20) or inhibited by CD4 ϩ T cells (21) of the B cell-deficient mice. Therefore, the approach we used to reconstitute B cell-depleted mice with B cells was to stop the anti-IgM treatment at various times (1-3 wk) after birth and allow peripheral B cells (B220 and IgM ϩ cells) to gradually repopulate the mice.…”

Section: B Cells Are Required Early In Life Before the Development Ofmentioning

confidence: 99%

Early Requirement for B Cells for Development of Spontaneous Autoimmune Thyroiditis in NOD.H-2h4 Mice

Braley‐Mullen

2000

The Journal of Immunology

126

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B cells are known to play an important role in the pathogenesis of several autoimmune diseases. NOD.H-2h4 mice develop spontaneous autoimmune thyroiditis (SAT) and anti-mouse thyroglobulin (MTg) autoantibodies, the levels of which correlate closely with the severity of thyroid lesions. NOD.H-2h4 mice genetically deficient in B cells (NOD.Kμnull) or rendered B cell-deficient by treatment from birth with anti-IgM develop minimal SAT. B cells were required some time in the first 4–6 wk after birth, because NOD.Kμnull or NOD.H-2h4 mice did not develop SAT when they were reconstituted with B cells as adults. The requirement for B cells was apparently not solely to produce anti-MTg autoantibodies, because passive transfer of anti-MTg Ab did not enable B cell-deficient mice to develop SAT, and mice given B cells as adults produced autoantibodies but did not develop SAT. B cell-deficient mice developed SAT if their T cells developed from bone marrow precursors in the presence of B cells. Because B cells are required early in life and their function cannot be replaced by anti-MTg autoantibodies, B cells may be required for the activation or selection of autoreactive T cells. These autoreactive T cells are apparently unable to respond to Ag if B cells are absent in the first 4–6 wk after birth.

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“…We utilized GalT −/− ,l −/− adoptive recipients for these studies in order to avoid absorption of anti-Gal Ab on Gal +/+ cells of adoptive recipients. Since CD4 + T cells derived from l −/− mice inhibit B cell engraftment (7,22), CD4…”

Section: Hyporesponsiveness Is Reversed By Donor Galmentioning

confidence: 99%

Differing Mechanisms of Early and Late B Cell Hyporesponsiveness Induced by Mixed Chimerism

Kawahara

Shimizu

Ohdan

et al. 2005

American Journal of Transplantation

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CD4⁺T cells derived from B cell-deficient mice inhibit the establishment of peripheral B cell pools

Cited by 34 publications

References 45 publications

Peritoneal Cavity B Cells Are Precursors of Splenic IgM Natural Antibody-Producing Cells

Peritoneal Cavity B Cells Are Precursors of Splenic IgM Natural Antibody-Producing Cells

Early Requirement for B Cells for Development of Spontaneous Autoimmune Thyroiditis in NOD.H-2h4 Mice

Differing Mechanisms of Early and Late B Cell Hyporesponsiveness Induced by Mixed Chimerism

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CD4+T cells derived from B cell-deficient mice inhibit the establishment of peripheral B cell pools

Cited by 34 publications

References 45 publications

Peritoneal Cavity B Cells Are Precursors of Splenic IgM Natural Antibody-Producing Cells

Peritoneal Cavity B Cells Are Precursors of Splenic IgM Natural Antibody-Producing Cells

Early Requirement for B Cells for Development of Spontaneous Autoimmune Thyroiditis in NOD.H-2h4 Mice

Differing Mechanisms of Early and Late B Cell Hyporesponsiveness Induced by Mixed Chimerism

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CD4⁺T cells derived from B cell-deficient mice inhibit the establishment of peripheral B cell pools